1. Field of the Invention
The present invention relates to a modified polysaccharide, to methods of synthesis and to methods of use in absorbing basic compounds such as urea from solution.
2. Description of the Prior Art
A sizable fraction estimated 50,000 people who die of kidney failure each year in the United States are free of other complications and might be restored to useful life if their kidney function could be provided artifically. At present, artificial kidneys (using hemodialysis) and clinical procedures have been developed to the point where long-term sustenance of life by periodic hemodialysis is practicable in many cases.
The limitations in using hemodialysis are the small number of patients who can be treated with a given kidney machine and the considerable expense of maintaining and staffing a kidney-treatment center. Obviously, a desirable solution lies in the development of an artificial kidney which is inexpensive, portable and capable of being operated outside the confines of a hospital with a minimum of medical attention. Attainment of this solution will require increased efficiency of mass transfer and further optimization in design of artificial-kidney systems.
In recent years, considerable attention has been focused on methods of reducing the size of the artificial kidney. This requires miniaturization of the membrane-containing dialyzer and a significant reduction in the volume of dialyzing fluid. It is generally conceded that the toxin primarily responsible for the uremic syndrome has not yet been identified. Even though urea is not considered particularly toxic, its removal is one of the chief objectives of dialysis as practiced today. The reason for the concentration on urea reomval is that, in the absence of more specific knowledge, dialysis based on this principle is obviously beneficial. At least two explanations suggest themselves: (a) Unidentified toxicants are removed along with the urea. (b) Urea produces toxic products.
In order to increase the efficiency of hemodialysis, it is desirable to maintain the trans-membrane concentration gradient of waste metabolites as high as possible. Low waste concentrations in the dialyzing fluid have in the past been maintained by two methods. The more widely used method is the continual dilution of the dialyzed substances in a large reservoir fluid, usually 100 to 300 liters. A second method of maintaining the gradient is to use the dialyzing fluid in a single-pass operation, where the waste-bearing effluent is discarded. Even then, more than 100 liters of fluid are required. The current research trend in obtaining low concentrations of wastes is to remove them selectively from the dialyzing fluid. Such an approach would allow the use of much smaller volumes of dialyzing fluid. Among all waste products, urea is by far the major waste metabolite which must be removed daily from the body fluid. Three major methods of urea removal from dialysate have been reported.
The first procedure utilizes an activated carbon bed which removes urea by absorption. However, the demonstrated capacity for urea is only 0.2-0.8 grams per 100 grams of carbon. In another method urea is reduced by enzymatic hydrolysis either inside microcapsules or by the combination with other absorbents. A commercial apparatus utilizes sodium zirconium phosphate to remove the ammonia produced by enzymatic decomposition of urea in the presence of urease. However, the capacity of urea removal is limited by the reaction extent of enzymatic decomposition.
It has recently been reported that oxystarch has been used for binding urea in its transit through the gastrointestinal tract (an in vivo application). Oxystarch is receiving wide attention for its potential as an absorber in the gastrointestinal tract. The disappointing aspect about this material is that it is useless in diaylsate because it dissolves in that fluid. Oxystarch absorbs urea at low pH but will dissolve if treated with alkali at pH 8. Therefore, oxystarch will dissolve into dialysate or leach into the blood if utilized for in vivo applications.